P1068: UPDATED RESULTS FROM AN OPEN-LABEL PHASE 1/2 STUDY OF FAVEZELIMAB IN COMBINATION WITH PEMBROLIZUMAB IN PATIENTS WITH RELAPSED OR REFRACTORY CLASSICAL HODGKIN LYMPHOMA AFTER ANTI–PD-1 TREATMENT
Authors: John Timmerman, David Lavie, Nathalie Johnson, Abraham Avigdor, Peter Borchmann, Charalambos Andreadis, Ali Bazargan, Gareth Gregory, Colm Keane, Inna Tzoran, Vladan Vucinic, Pier Luigi Zinzani, Rachel Marceau West, Pallavi Pillai, Patricia Marinello, Alex F. Herrera
Journal: HemaSphere (2023)

Topic: 17. Hodgkin lymphoma - Clinical Background: Programmed death 1 (PD-1) inhibitors are standard of care for relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL), but optimized treatment strategies are needed for patients (pts) with progressive disease after anti–PD-1 therapy. Dual blockade of PD-1 and lymphocyte-activation gene 3 (LAG-3) has demonstrated antitumor activity, leading to FDA approval of the combination in unresectable or metastatic melanoma. Favezelimab, a humanized IgG-4 LAG-3 inhibitor, plus pembrolizumab (anti–PD-1) is being investigated in a phase 1/2 efficacy and safety study (NCT03598608) in pts with R/R hematologic malignancies. Initial results showed effective antitumor activity and tolerable safety of pembrolizumab 200 mg QW3 and favezelimab 800 mg QW3 in heavily pretreated pts with R/R cHL whose disease progressed after anti–PD-1 therapy (cohort 2; Timmerman J et al. J Clin Oncol. 2022;40(16 suppl):7545). Aims: Evaluate efficacy and safety of favezelimab + pembrolizumab in pts with R/R cHL whose disease progressed after anti–PD-1 therapy. Methods: Eligible pts in cohort 2 had R/R cHL after autologous stem cell transplantation (ASCT) or were ineligible for ASCT or did not respond to salvage chemotherapy, an ECOG PS ≤1, and disease progression after ≥2 doses of anti–PD-1-based therapy. In part 1 (safety lead-in), pts from all cohorts received favezelimab IV 200 mg or 800 mg Q3W plus pembrolizumab IV 200 mg Q3W. Dose finding based on occurrence of dose-limiting toxicities (DLTs) was determined using a modified toxicity probability interval design. In part 2 (dose expansion), pts received pembrolizumab plus favezelimab at the established RP2D (800 mg Q3W) for ≤35 cycles (~2 years). Primary end points were safety and RP2D. Secondary end points included ORR. Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were exploratory. Results: Cohort 2 enrolled 34 pts. Median age was 37.5 years, 62% had ECOG PS of 0, and 94% had ≥4 prior lines of therapy; 17 pts (50%) had an anti–PD-1–based regimen as their most recent line of therapy. At database cutoff (August 31, 2022), 8 pts (24%) had completed 2 years of study treatment and 25 (74%) had discontinued (including 13 because of progressive disease and 7 because of adverse events). After a 29.3-month (range, 9.0-43.4) median follow-up (first dose to data cutoff), 10 pts had an objective response (ORR, 29% [95% CI, 15-48]; complete response [CR], 3 [9%]; partial response [PR], 7 [21%]). 25 of 28 pts (89%) with a postdose scan had reduction in target lesion size from baseline, and 12 pts (43%) had ≥50% reduction from baseline. Median DOR was 21.9 months (range, 0.0+ to 24.0); an estimated 52% of responders remained in response ≥15 months. Median PFS was 10.7 months (95% CI, 5.1-14.7); 15-month PFS rate was 33%. Median OS was not reached (NR; 95% CI, 25.7-NR); 15-month OS rate was 87%. Of the 10 responders, 7 had ≥5 prior lines of therapy (CR, 3; PR, 4); 3 responders (all PR) had ≤4 prior lines of therapy. Among 28 pts (82%) who had a treatment related AE the most common (≥15%) were hypothyroidism and nausea (18% each), diarrhea and fatigue (15% each). Grade 3 or 4 treatment related AEs occurred in 6 pts (18%). No deaths were treatment related. 1 patient who received allogeneic hematopoietic stem cell transplantation after completion of study treatment had a grade 3 AE unrelated to study treatment that resolved. Summary/Conclusion: The combination of favezelimab plus pembrolizumab continued to demonstrate antitumor activity and manageable safety in pts with R/R cHL whose disease progressed following anti–PD-1 therapy. Keywords: Clinical trial, Immunotherapy, Hodgkin’s lymphoma